Gastrointestinal germinal center B cell depletion and reduction in IgA <sup>+</sup> plasma cells in HIV-1 infection
Gastrointestinal (GI) B cells and plasma cells (PCs) are critical to mucosal homeostasis and the host response to HIV-1 infection. Here, high-resolution mapping of human B cells and PCs sampled from the colon and ileum during both viremic and suppressed HIV-1 infection identified a reduction in germinal center (GC) B cells and follicular dendritic cells (FDCs) during HIV-1 viremia. Immunoglobulin A-positive (IgA<sup>+</sup>) PCs are the major cellular output of intestinal GCs and were significantly reduced during viremic HIV-1 infection. PC-associated transcriptional perturbations, including type I interferon signaling, persisted in antiretroviral therapy (ART)-treated individuals, suggesting ongoing disruption of the intestinal immune milieu during ART. GI humoral immune perturbations were associated with changes in the intestinal microbiome composition and systemic inflammation. These findings highlight a key immune defect in the GI mucosa due to HIV-1 viremia.
Authors
- Francesca Cossarini (ORCID: https://orcid.org/0000-0002-8793-5241)
- K. N. Sharma (ORCID: https://orcid.org/0000-0001-6888-6205)
- Ruixue Hou (ORCID: https://orcid.org/0000-0002-6423-651X)
- Alexandros D. Polydorides (ORCID: https://orcid.org/0000-0001-8604-0756)
- Gustavo Martínez-Delgado (ORCID: https://orcid.org/0000-0003-4655-3770)
- Arno R. Bourgonje (ORCID: https://orcid.org/0000-0001-5754-3821)
- Zainab Al-Taie (ORCID: https://orcid.org/0000-0003-2624-2035)
- Benjamin K. Chen (ORCID: https://orcid.org/0000-0002-5404-1997)
- Mathieu Uzzan (ORCID: https://orcid.org/0000-0002-7761-2879)
- Ivan Vujkovic-Cvijin (ORCID: https://orcid.org/0000-0002-8611-4900)
- Andrea Cerutti (ORCID: https://orcid.org/0000-0003-3026-4704)
- Joan Shang (ORCID: https://orcid.org/0000-0001-8274-1109)
- Darwin D’souza (ORCID: https://orcid.org/0000-0002-1943-5173)
- Azra Krek (ORCID: https://orcid.org/0009-0001-7845-9984)
- Divya Jha (ORCID: https://orcid.org/0000-0002-5038-241X)
- Giorgio Ioannou (ORCID: https://orcid.org/0000-0001-7956-7605)
- Jeremiah J. Faith (ORCID: https://orcid.org/0000-0002-2691-4500)
- Saurabh Mehandru (ORCID: https://orcid.org/0000-0001-9781-2969)
- Minami Tokuyama (ORCID: https://orcid.org/0000-0001-6488-9687)
- Seunghee Kim‐Schulze (ORCID: https://orcid.org/0000-0003-0192-4400)
- Michael Tankelevich
- Carmen Argmann (ORCID: https://orcid.org/0000-0002-1110-8012)
- Louise Leyre (ORCID: https://orcid.org/0000-0002-7890-702X)
- Pablo Canales-Herrerías (ORCID: https://orcid.org/0000-0002-1865-6476)
- Mayte Suárez‐Fariñas (ORCID: https://orcid.org/0000-0001-8712-3553)
- Sacha Gnjatic (ORCID: https://orcid.org/0000-0001-5643-9520)
- Alexandra E. Livanos (ORCID: https://orcid.org/0000-0002-8418-3400)
- Francesca Petralia (ORCID: https://orcid.org/0000-0001-5096-9854)
- Travis Dawson (ORCID: https://orcid.org/0000-0002-9609-793X)
- Judith A. Aberg (ORCID: https://orcid.org/0000-0001-8162-0284)
- Douglas S. Kwon (ORCID: https://orcid.org/0000-0001-8521-8735)
- Ahmed Akm
- Mabel Cruz (ORCID: https://orcid.org/0009-0006-1408-0840)
- Martha L. Taylor (ORCID: https://orcid.org/0009-0001-8002-3506)
- Adam Tillowitz (ORCID: https://orcid.org/0000-0001-6702-4048)
Institutions
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Cedars-Sinai Medical Center (US)
- Ragon Institute of MGH, MIT and Harvard (US)
- Centre Hospitalier Universitaire Henri-Mondor (FR)
- Massachusetts General Hospital (US)
- Hôpitaux Universitaires Henri-Mondor (FR)
- Hospital Del Mar (ES)
- Hospital del Mar Research Institute (ES)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Science Immunology
- Published
- 2024-10-25
- DOI
- https://doi.org/10.1126/sciimmunol.ado0090
- Citations
- 4
- Primary Topic
- HIV Research and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 1.17
Funders
- U.S. Department of Health and Human Services
- Bill and Melinda Gates Foundation
- National Institutes of Health
- National Institute of Mental Health
- National Institute of Allergy and Infectious Diseases